The long-term goal of this research is to discover the function(s) of sleep. This knowledge would help to understand the role of sleep loss in illness, the role of sleep in recovery, and proper sleep hygiene. The function could be revealed in the effects of sleep deprivation. Chronically sleep deprived rats show a stereotypic syndrome: weight loss in spite of increased food intake, skin pathology, increased plasma norepinephrine, decreased plasma thyroxin (but increased conversion to its active form), a decline in body temperature, and eventual death. Two pathological processes could mediate many of these symptoms--excessive energy expenditure and excessive heat loss. The first could be compensatory for the second. Proposed studies will evaluate putative mediators of the syndrome. To evaluate whether sympathetic activation mediates excess energy expenditure, effects of sympathetic blockade on development of the syndrome will be determined. To evaluate whether the thyroid system mediates excess energy expenditure, the effect of blocking thyroxin synthesis on development of the syndrome will be determined. If either procedure blocks increases in energy expenditure but hastens the temperature decline, then excess energy expenditure would emerge as a secondary symptom which compensates for excessive heat loss. To evaluate whether an unknown bloodborne calorigenic substance mediates the increased energy expenditure, the blood of sleep deprived rats will be circulated through selected organs of recipient rats while metabolic rate in these organs is measured. To evaluate whether sleep deprivation causes excessive heat loss, sleep deprived rats and their yoked controls will be compared on behavioral thermoregulation (excessive heat loss should increase heat-seeking behavior); body temperature response to heat and cold exposure (excessive heat loss should cause a relatively large decrease in the cold); and the coupling of peritoneal and hypothalamic temperatures (excessive heat loss would likely cause larger declines in peritoneal than in hypothalamic temperature). These studies would also indicate whether central or peripheral failures mediated any excessive heat loss.